Genetically animals provide a unique way to integrate information gained at the molecular level with behavioral studies. Protein kinase A (PKA) plays an important role both in the cellular processes thought to underlie memory and in behavioral tests of memory. In this proposal, the role of PKA in memory will be further defined using a temporally regulated and spatially restricted of PKA in memory will be further defined using a temporally regulated and spatially restricted transgenic mouse approach. In Specific Aim 1, transgenic mice with a tetracycline regulated transgene encoding R(AB), a dominant inhibitor of PKA, will be generated. In Specific Aim 2, the temporal control of R(AB) expression will be used to define the role of PKA in the consolidation, retrieval, and extinction of spatial and contextual memory. Specific Aim 3 will examine the importance of PKA in non-aversive hippocampus-dependent memory tasks. This research using regulated transgenic approaches will help define the cellular and molecular mechanisms of long-term memory storage and enhance our understanding of a variety of neurological and mental disorders including Alzheimer's disease, mental retardation, and depression in which PKA is thought to play a critical role.